Keywords: Functional Connectivity, Psychiatric Disorders, MDD, FCS, Neurotransmitters
Motivation: The differences between first-episode drug-naïve (FEDN) and recurrent major depressive disorder (RMDD) patients in the functional dysconnectivity and their association with neurotransmitter systems remain poorly understood.
Goal(s): To investigate distance-specific alterations of functional connectivity (FC) and the relationship between functional dysconnectivity and neurotransmitter systems in MDD subtypes.
Approach: We examined distance-dependent FC differences in a large cohort of 848 MDD patients and 794 controls, and integrated them with neurotransmitter density from a public PET dataset.
Results: FEDN and RMDD showed distinct patterns of distance-dependent FC disruption, particularly in long-range connections, with specific correlations with serotonergic, GABAergic, and opioid systems.
Impact: Functional dysconnectivity in MDD subtypes shows distinct distance-dependent patterns and specific correlations with neurotransmitter systems. These findings advance our understanding of subtype-specific pathophysiology and may guide the development of more precise therapeutic strategies for MDD.
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